PROJECT SUMMARY There are over 1.5 million state and federal prisoners in the U.S., and the rate of drug use disorders among inmates far exceeds that of the general population (50% versus 2%). Opioid relapse occurs at high rates following release from incarceration, and opioid overdose is the leading cause of death among former prisoners, the risk for which is especially high within the first week following release. Additionally, relapse is associated with increased risk of violent behavior and criminal activity, and thereby recidivism, as well as many other adverse personal and social consequences that, in total, cost the U.S. over $93 billion each year. Of notable concern is that the high-risk population of pre-release prisoners with an opioid use disorder (OUD) has limited or, frequently, no access to evidence-based OUD therapy. Extended-release naltrexone (XR-NTX; Vivitrol) is uniquely positioned to have a high impact on this population, and on public health. Of the 3 FDA-approved pharmacotherapy options for OUD, naltrexone appears to face the fewest potential preferential and legislative barriers to use in prison systems. Moreover, the extended-release formulation blocks opioids for 30 days, thereby giving the ex-inmate ?protected time? upon release. However, at a cost of up to $1,309 per injection, the legislators who set prison healthcare budgets, and the prisons who operate on limited budgets, may be reluctant to fund XR-NTX without evidence of both improved health outcomes and downstream cost-offsets (e.g., from reduced criminal activities and use of high-cost, publicly-funded, healthcare services), which our review of the literature indicates effective therapy is capable of producing. Our previous work among a community-dwelling criminal-justice population showed XR-NTX to be effective at increasing time abstinent from opioids, reducing opioid relapse and overdose deaths, and increasing health-related quality-of-life (HRQoL). We did not find significant differences in the utilization of non-study healthcare services; however, it is unlikely that the study population was representative of the high-risk population of pre-release prisoners. The trial included community- dwelling individuals who were opioid-free at enrollment, and the inclusion criteria did not require incarceration. This project offers a unique opportunity to greatly expand our understanding of the impact of XR-NTX in this context. We will use data from 2 publicly-funded randomized controlled effectiveness trials in which XR-NTX is being evaluated among pre-release prisoners with OUD, to evaluate whether XR-NTX is associated with changes in the healthcare service utilization, enhanced patient wellbeing, and economic viability from policy- maker and societal perspectives. We will not only be able to assess differences in these secondary outcomes between study arms within each trial ([XR-NTX vs. treatment as usual] and [enhanced XR-NTX with mobile medical XR-NTX treatment post-release vs. XR-NTX]), but also to merge the data sets and test for differences across trials. Finally, we will have the unprecedented opportunity to measure HRQoL among prisoners with OUD prior to their release, and track changes in their HRQoL following their release and treatment engagement.